Background: Major depressive disorder is usually
a recurring illness, and maintenance treatment is used to
forestall or prevent recurrent episodes of depression. This study
describes recurrence of major depression despite maintenance
pharmacotherapy, termed tachyphylaxis.

Method: The study sample consisted of 103
subjects who participated in the NIMH Collaborative Depression
Study, a multicenter longitudinal observational study of the mood
disorders. Subjects diagnosed with unipolar major depressive
disorder according to Research Diagnostic Criteria were enrolled
from 1978-1981 and prospectively followed for up to 20 years. As
an observational study, treatment was recorded but not controlled
by anyone connected with the study. Subjects were selected for
the present study if at some point during follow-up they received
antidepressant medication for treatment of an episode of major
depressive disorder, recovered from this episode, and
subsequently received maintenance pharmacotherapy. Some subjects
were successfully treated for multiple episodes of major
depressive disorder and then received maintenance medication
after each of these episodes, resulting in multiple maintenance
treatment intervals. Data were collected using the Longitudinal
Interval Follow-Up Evaluation, and mixed-effects logistic
regression was used to test the association of sociodemographic
and clinical variables with tachyphylaxis.

Results: For the 103 subjects, there were 171
maintenance treatment intervals in which a subject received
maintenance pharmacotherapy after having recovered from an
episode of major depressive disorder. The median duration of
maintenance treatment was 20 weeks. Tachyphylaxis occurred during
43 (25%) of these 171 maintenance treatment intervals. The
subtype of melancholic (endogenous) major depressive disorder
significantly elevated the risk of tachyphylaxis during the
subsequent maintenance treatment interval.

Conclusions: Despite the use of maintenance
pharmacotherapy, major depression recurs in a considerable number
of patients. Improved prophylaxis for these patients requires
other treatment strategies based upon a greater understanding of
recurrence.